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NCT Number: NCT02888964

Pioglityazone and Imatinib for CML Patients

This project is a Phase II clinical trial that aims at evaluating efficacy and tolerance of the combination of pioglitazone (Actos®) and imatinib mesylate (STI571, CGP57148, Gleevec®) in patients with Chronic Myelogenous Leukemia (CML) in stable major molecular response (i.e. a BCRABL/ABL ratio assessed by RTQ-PCR equal to or lower than 0.1% according to the European Leukemia Net recommendations) after at least 2 years of therapy with imatinib.

Imatinib mesylate (Gleevec®) is the gold standard for the treatment of CML in chronic phase (O Brian et al. 2003, Druker et al. 2006). Despite a high efficacy of the drug, CML is not eradicated by imatinib alone in almost any of the patients.

Treatment discontinuation in patients treated by imatinib and in complete molecular remission for more than 2 years yield molecular relapses within 6 months in half of the patients,indicating the persistence of CML progenitor cells. STAT5 expression is required for CML stem cell engraftment and expansion in mouse models. STAT5 is the target of the dysregulated activity of BCR-ABL in CML.

Recently, Stephane Prost et al. demonstrated that PPAR-γ is a negative regulator of STAT5A and STAT5B gene expression. Data obtained suggest that PPAR-γ agonists may have potential therapeutic value in reversing myeloproliferative disorders. On the basis of our preclinical studies, we went ahead and administered pioglitazone to one patient who suffered from both diabetes type II and CML with residual disease after continuous treatment with Gleevec. The amount of BCR-ABL transcript detected by QPCR decreased dramatically during the first 3 months of combined (Gleevec + ACTOS) therapy to become undetectable thereafter until 9 months post-treatment, the latest time point assessed. This striking anecdotal result now forms the rationale for filing this formal Phase II clinical trial application.

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Key information

Conditions

Leukemia, Myeloid, Chronic-Phase Bone Marrow Diseases Chronic Disease Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

CHR Annecy, Annecy, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patient aged 18y or more
  • Signed informed consent
  • Patient with Philadelphia chromosome positive chronic phase CML and M BCR-ABL transcript positivity
  • Treatment with imatinib for more than 2 years
  • No dose modification of imatinib within the last 3 months
  • Complete cytogenetic response on the last cytogenetic analysis within the last 12 months
  • Major molecular remission without complete molecular remission
  • ECOG grade 0 to 2
  • SGOT et SGPT ≤ 2.5 N
  • Bilirubin in serum ≤ 1.5 N
  • Women of childbearing potential (WOCBP) must be using an adequate method of contraception

Exclusion criteria

  • Participation in another clinical trial with any investigative drug within 30 days prior to study enrollment
  • Prior history of hematopoietic stem cell transplantation (autologous or allogenic)
  • Patient requiring anti-diabetic medication
  • Cardiovascular disease:
  • Stage I to IV congestive heart failure (CHF) as determined by the New York Heart Association (NYHA) classification system for heart failure
  • Myocardial infarction within the previous 6 months
  • Symptomatic cardiac arrhythmia requiring treatment
  • Grade III or IV fluid retention
  • Known osteoporosis with therapy

Treatment and study plan

Add-on therapy

Drug

Pioglitazone therapy

Primary outcomes

  1. The rate of patients achieving a complete molecular response (Sensitivity 10-5 or Bcr Abl/Abl ratio < 0.001 %) 24 weeks after the initiation of pioglitazone, confirmed on by a second determination 2 months later.

    Time frame: 26 weeks

Secondary outcomes

  1. Adverse events

    Time frame: 5 years

  2. Duration of the complete molecular response

    Time frame: 5 years

  3. The rate of patients achieving a complete molecular response (Sensitivity 10-5 or Bcr-Abl/Abl ratio < 0.001 %)

    Time frame: 14 months

  4. Survival

    Time frame: 5 years

  5. Progression free survival

    Time frame: 5 years

Sponsors and collaborators

Lead sponsor

Versailles Hospital

Other

Registry information

Official study title

A Study to Assess Efficacy and Safety of Pioglitazone as Add-On Therapy to Imatinib Mesylate in CP-CML Patients in Major Molecular Response

Acronym: ACTIM

Important dates

Study start
2009
Primary completion
2012
Study completion
2016
First posted
Sep 5, 2016
Registry last updated
Jul 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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